progression and treatment of RA

• compare inflammatory and non-inflammatory Arthritis

  here

  
• Rheumatoid arthritis is the most common arthritis in the UK (T/F)

  false
• Rheumatoid arthritis can affect all synovial joints in the body (T/F)

  true
• Rheumatoid arthritis hereditary (T/F)

  false
• Rheumatoid always presents with  symmetrical joint involvement (T/F)

  false
• pattern of joint involvement in RA

  DIPs spared

  MTPJ are more load bearing and this could be why they are affected so much

  
• typical presentation:

  Sub-acute onset of:

  • Pain and stiffness hands, wrists, feet +/- large  joints

  • 1 hour morning stiffness

  •  +/- Joint swelling – eg difficulties with rings

  • Undue fatigue

  • Difficulties with certain activities – opening jars +  bottles, keys, typing

  • In some cases, more prominent systemic  symptoms –eg weight loss
• Specific features to ask about in  history (why?)

  •Skin problems–Scaly rash; photosensitive rash; rash on face ( SLE )

  •Eye problems–Grittiness; acute red eyes; red eye + blurred vision ( uveitis -> seronegative arthritis )

  •Dry mouth ( Sjogren's syndrome - dry mouth and eyes)

  •Alopecia ( SLE )

  •Raynaud’s (Lupus)

  •Preceding illnesses (eg viral illness)

  •Family history
• Mono arthritis- one joint, diff dx septic arthritis

  Poly arthritis- 4 or more

  Oligoarthritis 2-3
• DIFFERENTIAL DX

  SLE – butterfly rash, symmetrical joint involvement

  Juvenile inflammatory arthritis

  Gout

  Enteropathic arthritis / spondyloarthritis

  Psoriasis – psoriatic arthritis commonly affect DIPJS and sometimes exclusively that

  Ankolysing spondylitis
• Examination findings 1: general

  • May be normal

  • Or there may be:

  – Anaemia

  – Lymphadenopathy

  – Palmar erythema

  • NB Look for rashes (+scalp), nail dystrophy, tophi

  – possible indications of alternative diagnosis
• Examination findings 2: Joints

  • Articular tenderness

  – Especially proximal interphalangeal,  metacarpophalangeal, wrists, metatarsophalangeal

  • Soft tissue swelling of joints +/- effusions

  • Functional impairment

  – Diminished grip strength

  – Impaired fist formation

  – Inability to extend elbows fully
• signs / symptoms:

  • ulnar deviation sign of long term damage
  • swan neck
  • boutonniere (squaring of the thumb)
  • note tar staining may indicate smoker
  • painful , warm joints
  • Tophi
  • rheumatic nodules

  here

  
• Lab investigations:

  • Full blood count – man see anaemia which is common in RA

  • ESR (erythrocyte sedimentation rate) – elevated -> inflammatory process indicated

  • CRP (C reactive protein) – elevated -> inflammatory process indicated

  • Autoantibodies serology - ACPA positive (more sensitive and specific), RF positive

  • Urea and electrolytes – possible systemic effects of RA?

  • Liver function tests – effect of DMARDs

  • Serum urate - shown to be a good indicator of Gout , possibly RA

  • Consider Thyroid function, glucose
• non-lab diagnosis and investigation:

  •  X-rays show soft tissue swelling, but ultrasound and MRI are useful to demonstrate synovitis and early erosions.
  • Aspiration of the joint if an effusion is present. The aspirate looks cloudy due to white cells. In a suddenly painful joint, septic arthritis should be suspected.
  • Musculoskeletal ultrasound effective way of demonstrating persistent synovitis when deciding on the need for DMARDs or assessing their efficacy.
• urea and electrolyte:

  K+ , Na+ , urea , creatinine
• Rheumatoid Factor predicts worse disease (T/F)


  true
• IgM RF is what is usually measured (T/F)

  true
• Rheumatoid factor is more sensitive and specific than anti CCP (T/F)

  false
• •30% of patients may be RF negative

  true
• Sensitivity = a / a + c

  Specificity = d / b + d

  here

  
• where else is RF found?

  • 2-4 % of the normal population
  • other autoimmune diseases : primary Sjogren's syndrome , SLE
  • chronic infections : TB
  • some viral infections ( Epstein Barr virus )
  • B cell proliferative diseases
• • Anti CCP (anti-cylcic citrullinated peptide)

  – Some prognostic associations eg erosions

  – May be positive years before arthritis onset
• •Anti nuclear antibody (ANA)

  – Stronger association with SLE and other  connective tissue diseases but is seen in  patients with RA

  – Also in hepatic and pulmonary diseases,  infections, malignancies

  – Also low positives in normals
• •Chest X ray

  – look for conditions which may present with joint symptoms (eg sarcoidosis, lung cancer )

  – look for RA lung involvement

  •Hands and Feet

  – Tend to be earliest to show RA changes

  – Early changes: soft tissue swelling, juxta-articular osteopaenia

  – Erosions – classical RA feature (generally irreversible)
• bone erosion ( e.g. wrist erosion ) by the hypervascularised synovium
• ultrasound can detect:

  • synovitis
  • tenosynovitis
  • erosions
• diagnosing RA, which is true

  • Blood tests are essential in the diagnosis of RA
  • X-rays are the gold standard in diagnosis
  • Rheumatoid arthritis is a clinical diagnosis
  • History is more important than examination

  false

  false

  true

  false
• Uncontrolled RA results in:

  • Increasing joint damage and deformity

  • Increasing disability–High incidence of patients unable to work  after 5 yrs RA

  • Increased mortality–inflammatory impact on cardiovascular system (+ classic cardiovascular risk factors)
• subluxation of joints may be seen in RA , the joints are worn out , loose and stretched due to inflammation and it is easier for joints in the bone to move
• One of the earliest manifestations of RA is painful swelling of the MTP joints.

  • foot becomes broader and a hammer-toe deformity develops.
  •  Exposure of the metatarsal heads to pressure by the forward migration of the protective fibrofatty pad ( Fig. 18.24 ) causes pain.
  •  Ulcers or calluses may develop under the metatarsal heads and over the dorsum of the toes.
  • broad, deep, cushioned shoes are essential
  • walking is painful and limited. Podiatry helps and surgery may be required.
  •  Mid- and hindfoot RA causes a flat medial arch and loss of flexibility of the foot.
  • valgus ankle.

  
• Multi-disciplinary team to help:

  •Control symptoms

  •Minimise impact

  •Minimise joint damage

  •Maximise function
• symptomatic treatment of RA:

  • Analgesics

  –Simple and compound

  • Non steroidal anti-inflammatory drugs  (NSAIDs)–Help control symptoms

  –No impact on progression of underlying  arthritis

  –Significant side effects

  – GI, CVS, Renal
• Disease Modifying Anti-Rheumatic  Drugs (DMARDs)

  • Improve symptoms and tests of inflammation

  • May slow the progression of the arthritis

  • Heterogeneous group of drugs (mechanism of  action in RA often unknown)

  • All take weeks-months to act

  • All have potential serious side effects requiring  monitoring tests (eg blood tests, urine tests, BP)
• list 3 commonly used DMARDs:

  • methotrexate - first line but not for pregnant women
  • sulfasalazine
  • hydrochloroquine

  here

  
• DMARD therapy in early RA

  • The “window of opportunity”

  • Early aggressive treatment

  – Rapid control of inflammation

  – “Treat to Target”

  – Intra-articular +/or short term systemic  steroids
• Corticosteroids in RA

  • Can be used orally, by intra-articular,  intramuscular, intravenous injection

  • A double edged sword

  – Provide relief of inflammation

  – Long term use associated with side effects

  •Osteoporosis, skin atrophy, increased infections  etc
• Biologic agents in RA

  • Agents targeting specific immune molecules  (eg TNF, IL-6) or cells (eg CD20)•Include monoclonal antibodies

  • Parenteral administration

  • Expensive (NICE approved)

  • Have revolutionised the lives of some patients

  • An expanding repertoire
• Anti-Tumour Necrosis Factor  (Anti-TNF)

  • An increasing number of agents available

  • NICE have defined when they should be used

  • Was £10k/patient/year- now off patent

  • Well tolerated–some uncertainty re long term side effects.–In practice small increase in serious infections
• other targeted therapies for RA:

  • Anti-CD20 (Rituximab)

  – B-cell depletion

  6 monthly infusions

  • Anti-IL6 (Tocilizumab)

  S/C injections

  • Co-stimulation inhibitor (Abatacept)

  S/C injections

  • JAK inhibitors  (e.g. Baricitinib)

  Daily tablets